Mitochondrial monoamine oxidase (MAO) is being studied with respect to the structural factors responsible for differential substrate and inhibitor specificities in various tissues, in situ regulation factors relevant to metabolism of neurotransmitters in the CNS, and the relationship of blood platelet levels of the enzyme to mental disorders. ESR of spin label inhibitor analogs binding to the active site are being used to investigate mechanisms of substrate and inhibitor binding and to monitor conformational effects accompanying shifts in substrate specificity. Systematic membrane modification with synthetic phospholipids is being used to probe the role of lipid environment in MAO active site structure. Cyanide has been found to activate the enzyme and kinetic and binding studies of this activation are being pursued with regards to possible clues this phenomenon may provide to regulation and catalytic mechanisms. Monoclonal antibodies are being developed as a new approach to differentiating structural features that determine substrate specificity and for use in developing new clinical assays. Ongoing investigations concerning human platelet MAO and affective disorders, as well as studies of an animal model of the Fetal Alcohol Syndrome, are currently in progress.